This project includes a range of studies designed to elucidate the neurobiology of PTSD, panic disorder and social phobia, and to investigate potential new treatments for these serious anxiety disorders. Studies include neuroendocrine and behavioral challenges with the cholecystokinin agonist pentagastrin, treatment with standard and novel psychoactive drugs (serotonin reuptake inhibitors, gabapentin, lamotrigine), treatment trials with repetitive transcranial magnetic stimulation (rTMS), and positron emission tomography (PET) studies. Pentagastrin has been shown to induce severe anxiety and panic in patients with social phobia and panic disorder. Preliminary studies suggest that the panicogenic effect of pentagastrin generalizes to patients with post-traumatic stress disorder. Ondansetron, a 5-HT3 antagonist, does not interfere with the anxiogenic effects of pentagastrin, suggesting that contrary to what is suggested from animal studies, the anxiogenic effects of CCK agonists are not mediated via 5-HT3 receptors. Preliminary studies of right frontal 1 Hz rTMS for the treatment of post traumatic stress disorder suggest that it reduces symptoms of PTSD and leads to a reduction in hypermetabolism in paralimbic brain regions.